Synlett 2006(11): 1679-1682  
DOI: 10.1055/s-2006-944214
LETTER
© Georg Thieme Verlag Stuttgart · New York

Anodic Cyanation of (S)-(-)-1-(1-Phenylethyl)piperidine: an Expeditious Synthesis of (S)-(+)-Coniine

Nicolas Girard, Laurent Pouchain, Jean-Pierre Hurvois*, Claude Moinet
Laboratoire d’Electrochimie et Catalyse, UMR 6226, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
Fax: +33(2)23235967; e-Mail: Jean-Pierre.Hurvois@univ-rennes1.fr;
Further Information

Publication History

Received 28 March 2006
Publication Date:
04 July 2006 (online)

Abstract

A short and efficient asymmetric synthesis of enantiopure (S)-(+)-coniine is reported. Anodic cyanation of (-)-1-[(1S)-1-phenylethyl]piperidine, derived from [(1S)-1-phenylethyl]amine, results in regioselective formation of the corresponding α-amino­nitrile, which was alkylated with propyl iodide to give a bifunc­tional derivative. The latter underwent a stereoselective reductive decyanation (80% de), the product of which was hydrogenolyzed to afforded (S)-(+)-coniine (99% ee) with an overall 35% yield from (-)-1-[(1S)-1-phenylethyl]piperidine.

    References and Notes

  • For selected reviews, see:
  • 1a Fodor GB. Colasanti B. In Alkaloids: Chemical and Biological Perspectives   Vol. 3:  Pelletier SW. John Wiley; New York: 1985.  p.1 
  • 1b Schneider MJ. In Alkaloids: Chemical and Biological Perspectives   Vol. 10:  Pelletier SW. John Wiley; New York: 1996.  p.155 
  • 2a Laschat S. Dickner T. Synthesis  2000,  1781 
  • 2b Michael JP. Nat. Prod. Rep.  2001,  18:  520 
  • 2c Buffat MGP. Tetrahedron  2004,  60:  1701 
  • 3a Reding MT. Buchwald SL. J. Org. Chem.  1998,  63:  6344 
  • 3b Hong S. Kawaoka AM. Marks TJ. J. Am. Chem. Soc.  2003,  125:  15878 
  • 3c Gommerman N. Knochel P. Chem. Commun.  2004,  2324 
  • 3d Sattely ES. Cortez GA. Moebius DC. Schrock RR. Hoveyda AH. J. Am. Chem. Soc.  2005,  127:  8526 
  • 4a Katritzky AR. Qiu G. Yang B. Steel PJ. J. Org. Chem.  1998,  63:  6699 
  • 4b Guillauteau-Bertin B. Compère D. Gil L. Marazano C. Das BC. Eur. J. Org. Chem.  2000,  1391 
  • 4c Amat M. Llor N. Hidalgo J. Escolano C. Bosch J. J. Org. Chem.  2003,  68:  1919 
  • 4d Klegraf E. Follman M. Schollmeyer D. Kunz H. Eur. J. Org. Chem.  2004,  3346 
  • 4e Comins DL. Sahn JJ. Org. Lett.  2005,  7:  5227 
  • 4f Madan S. Milano P. Eddings DB. Gawley RE. J. Org. Chem.  2005,  70:  3066 
  • 5a Gawley RE. Zhang Q. J. Org. Chem.  1995,  60:  175 
  • 5b Gawley RE. Low E. Zhang Q. Harris R. J. Am. Chem. Soc.  2000,  3344 
  • 6a Enders D. Shilvock J.-P. Chem. Soc. Rev.  2000,  29:  359 
  • 6b Husson H.-P. Royer J. Chem. Soc. Rev.  1999,  28:  383 
  • 7a Santamaria J. Kaddachi MT. Synlett  1991,  739 
  • 7b Santamaria J. Kaddachi MT. Ferroud C. Tetrahedron Lett.  1992,  33:  781 
  • 8a Michel S. Le Gall E. Hurvois JP. Moinet C. Tallec A. Liebigs Ann./Recl.  1997,  2089 
  • 8b Girard N. Hurvois J.-P. Moinet C. Toupet L. Eur. J. Org. Chem.  2005,  2269 
  • 8c For a general review on electroorganic chemistry, see: Shono T. Tetrahedron  1984,  40:  811 
  • 9a Chiba T. Takata Y. J. Org. Chem.  1977,  42:  2973 
  • 9b See also: Yoshida K. Kitabayashi H. Bull. Chem. Soc. Jpn.  1987,  60:  3693 
  • 10 Yang T.-K. Yeh S.-T. Lay Y.-Y. Heterocycles  1994,  38:  1711 
  • 11 Tsuge H. Okano T. Eguchi S. Kimoto H. J. Chem. Soc., Perkin Trans. 1  1997,  1581 
  • 12 Papouchado L. Adams RN. Feldberg SW. J. Electroanal. Chem.  1969,  21:  408 
  • 13 Sassaman MB. Tetrahedron  1996,  33:  10835 
  • 14 For a recent review on coniine and hemlock alkaloids, see: Reynolds T. Phytochemistry  2005,  66:  1399 
  • 15a Guerrier L. Royer J. Grierson DS. Husson H.-P. J. Am. Chem. Soc.  1983,  105:  7754 
  • For recent enantioselective syntheses of (R)-(-)-coniine, see:
  • 15b Passarella D. Barilli A. Belinghieri F. Fassi P. Riva S. Sacchetti A. Silvani A. Danieli B. Tetrahedron: Asymmetry  2005,  16:  2225 
  • 15c Xu X. Lu J. Ge Z. Dong Y. Hu Y. Synlett  2004,  122 
  • For recent enantioselective syntheses of (S)-(+)-coniine, see:
  • 15d Yamashita Y. Mizuki Y. Kobayashi S. Tetrahedron Lett.  2005,  46:  1803 
  • 15e Burke AJ. Davies SG. Garner AC. McCarthy TD. Roberts PM. Smith AD. Rodriguez-Solla H. Vickers RJ. Org. Biomol. Chem.  2004,  2:  1387 
  • 15f Roa LF. Gnecco D. Galindo A. Terán JL. Bernès S. Tetrahedron: Asymmetry  2004,  15:  847 
  • 16 Hayes JF. Shipman M. Twin H. Chem. Commun.  2001,  1784 
17

Aminonitrile 3 readily decomposed on TLC plate, R f value is given for guidance.